fulltext

DOI 10.1393/ncc/i2019-19139-1

Colloquia_{: EuNPC 2018}

IL NUOVO CIMENTO 42 C (2019) 139

Preliminary results of the PASTA project

G. Pupillo(1)(∗), A. Fontana(2), L. Canton(3), F. Haddad(4), H. Skliarova(1), S. Cisternino(1), P. Martini(1), M. Pasquali(1), A. Boschi(5), J. Esposito(1), A. Duatti(5) and L. Mou(1)

(1) INFN, Laboratori Nazionali di Legnaro - Legnaro, Padova, Italy (2) INFN, Sezione di Pavia - Pavia, Italy

(3_{) INFN, Sezione di Padova - Padova, Italy}

(4_{) GIP ARRONAX and SUBATECH - Nantes, France}

(5) Universit`a di Ferrara - Ferrara, Italy

received 5 February 2019

Summary. — 67Cu,186Re and47Sc are theranostic radionuclides in the spot-light of the scientific community: the insufficient availability is limiting their use in clinical and pre-clinical studies. The aim of this work is the analysis of47_{Sc production by}

using high-energy and high-intensity cyclotrons, as the one installed at INFN-LNL in the framework of SPES project, by exploring promising nuclear reactions induced by proton-beams.

1. – Introduction

The worldwide increasing interest on theranostic radiopharmaceuticals, allowing the selection of patients with higher chance to respond to specific treatments and the ap-plication of individually customized dosimetry, is well represented by the recent Coordi-nated Research Project (CRP), promoted by the International Atomic Energy Agency (IAEA), focused on67_Cu, 186_{Re and} 47_{Sc as Emerging Theranostic Radionuclides (No.}

F22053) [1]. The aim of this work is the analysis of 47Sc production by using proton cyclotrons, as the one installed at INFN-LNL in 2015. The applied research in the field of nuclear medicine through the LARAMED project, acronym of LAboratory of RA-dionuclides for MEDicine, is currenty conducted in partnership with different italian and international research institutions, since the infrastructure at LNL (beam-lines and lab-oratories) is currently under construction. Cross section measurements are carried out at the ARRONAX facility (Nantes, France), where a 70 MeV cyclotron is operative and produces radionuclides for medicine [2]. Among the isotopes of interest for LARAMED and ARRONAX,47_{Sc is of particular interest for its great potential in theranostic but}

(∗) Corresponding author. E-mail: gaia.pupillo@lnl.infn.it

2 G. PUPILLOet al.

Fig. 1. – Photograph of the foils of a stacked-target.

also in radioimmunotherapy: its relatively long half-life (3.3492 d) permits to follow the slow biodistribution of monoclonal antibodies; the β− particles of low-medium energy (mean energy 162.0 keV; intensity 100%) are useful to deliver cytotoxic dose to small-medium sized tumours while the emitted γ−rays are suitable for SPECT or SPECT/CT cameras (energy 159.381 keV; intensity 68.3%). Moreover, β+ _{counterparts such as}44_Sc

or43_{Sc exist and may also allow the theranostic approach to be used with PET imaging.}

The PASTA project, acronym of Production with Accelerator of Sc-47 for Theranostic Applications, is focused on the production of47Sc by using enriched metal targets of48Ti,

49_Ti, 50_{Ti and} nat_{V metal targets. In fact, no experimental data are available for the} 49_Ti(p,x)47_{Sc reaction, while only few measurements were performed with the}48_{Ti and} 50_{Ti targets in oxide form [3]. In view of an optimized production, the co-production of}

contaminant radionuclides, especially the isotopic impurities that cannot be chemically separated from the desired product and affect the RadioNuclidic Purity (RNP), is a keypoint. For this reason, experiments are designed in order to measure not only the nuclear cross section of the radionuclide of interest (i.e. 47Sc), but also the production of isotopic contaminants (e.g. 46_{Sc) and other impurities (e.g.} 51_{Cr) that may affect the}

radiochemical procedure aimed at the radionuclide extraction and purification. 2. – Materials and Methods

Considering the high cost of the enriched metal powders49Ti and50Ti (natural abun-dance 5.41% and 5.18% respectively), first experiments at the ARRONAX facility were performed with nat_{V and} 48_{Ti (natural abundance 73.73%) metal targets, arranged in}

stacked-foils structures (fig.1). ThenatV metal foils were purchased by Goodfellow, while enriched48_{Ti metal targets were realized by using the High energy VIbrational Powders}

Plating (HIVIPP) method [4], to homogeneously deposit the enriched titanium powder (>99%, purchased by TraceScience) on an aluminium support. Considering the use of enriched expensive materials, a dedicated target holder ( 11 mm), a graphite collima-tor ( 9 mm) and a plastic support have been designed and realized at the INFN-LNL workshop and used to precisely define the beam size on target during these irradiation runs. The duration of a typical run was 1.5 h with a constant current of about 100 nA, monitored during the bombardment by using an instrumented beam dump.

In the meantime, a fruitful collaboration with experts in nuclear codes such as EM-PIRE, FLUKA and TALYS [5-7] started, in order to compare the different nuclear re-actions and identify the most promising energy region for 47Sc production. Among the radionuclidic impurities of 47_{Sc coproduced during the irradiation,} 46_{Sc (83.79 d}

half-life) causes the major concern since it is the only radioisotope with a longer half-life than

47_{Sc. For this reason, a cooling time after irradiation may only decrease the} 47_Sc/ 46_Sc

activity ratio: it is thus crucial to minimize as much as possible the46Sc production by carefully selecting the target material and the energy range. Aiming at this goal, the different nuclear codes are employed to estimate the cross sections to produce47_{Sc and} 46_{Sc by using the enriched and expensive material of interest (}49_{Ti and}50_Ti).

PRELIMINARY RESULTS OF THE PASTA PROJECT 3

Fig. 2. – Preliminary results of the48Ti(p,x)47Sc,46Sc nuclear cross sections (red dots).

3. – Results and Discussion

Figure 2 shows the preliminary results of the measurement of48_Ti(p,x)47_Sc,46_Sc

nu-clear cross sections (red dots). The reaction for 46Sc production shows a regular trend in the entire energy range investigated; on the contrary, the trend of the48_Ti(p,x)47_Sc

cross section is irregular at around 30-35 MeV; however, data anlysis is still in progress. Preliminary results of thenatV(p,x)47Sc, 46Sc cross sections are shown in fig.3 (red dots) and compared with previous measurements [3]. In both cases an overall good agreement can be found with previous measurements; however, in the energy range 50-60 MeV our values for47Sc production seems to be lower than previous data. For brevity, results regarding the production of44m_Sc,44_Sc,48_Sc,43_Sc,43_K,48_V,48_Cr,49_{Cr and}51_Cr

are not shown here; in case of44m_{Sc and}44_{Sc decay contribution was taken into account}

in the data analysis; for43_{Sc, the interference with the γ−ray at 373 keV emitted by}43_K

was corrected; in case of48Sc, the nuclear cross section is calculated by considering the γ−rays at 175 keV and 1037 keV, in order to avoid the interference with48_{V at the 938}

keV and 1312 keV γ−lines.

Figure 4 reports the theoretical estimations of47_Sc/46_{Sc cross section ratio for} 49_Ti

(left) and 50_{Ti (right) by using FLUKA (blue line), TALYS (red line) and EMPIRE}

4 G. PUPILLOet al.

Fig. 4. –47Sc/46Sc cross section ratio for49Ti (left) and50Ti (right) targets.

(brown line) nuclear codes. These estimations show that the nuclear reaction on 49_Ti

may be preferable than the nuclear reaction on 50Ti targets: in particular, the most promising energy range with 49_{Ti enriched material is 25-45 MeV; on the contrary, in}

case of50_{Ti targets the best energy range is at higher energies, i.e. E}

P > 40 MeV.

4. – Conclusion

This work reports preliminary results of the PASTA project, an interdisciplinary research activity that ranges from nuclear physics up to material science and radiochem-istry.

∗ ∗ ∗

This work was funded by INFN with the research project PASTA-Production with Accelerator of Sc-47 for Theranostic Applications (CSN5 Bando N. 18203, 2017-2018). It is developed in the framework of the CRP by IAEA (No. F22053) on Therapeutic Radiopharmaceuticals Labelled with New Emerging Radionuclides (67Cu, 186Re, 47Sc). It has been also, in part, supported by a grant from the French National Agency for Research called Investissements d’Avenir, Equipex Arronax-Plus (ANR-11-EQPX-0004) and Labex IRON (ANR-11-LABX-18-01).

REFERENCES

[1] IAEA, CRP, http://cra.iaea.org/cra/explore-crps/all-active-by-programme.html. [2] Haddad F. et al., Eur. J. Nucl. Med. Mol. Imaging, 35 (2008) 1377–1387. [3] EXFOR, Database, https://www-nds.iaea.org/exfor/exfor.htm.

[4] Sugai I. et al., Nucl. Instr. and Meth. A, 397 (1997) 81-90. [5] Herman M. et al., Nucl. Data Sheets, 108 (2007) 2655-2715. [6] Boehlen T.T. et al., Nucl. Data Sheets, 120 (2014) 211-214. [7] Koning A.J. et al., EDP Sciences, (2008) 211-214.